New Delhi, July 31, 2025 -- Eli Lilly and Company today announced topline results from  SURPASS-CVOT, a first-of-its-kind head-to-head Phase 3 cardiovascular outcomes trial  comparing two incretin therapies in adults with type 2 diabetes and established atherosclerotic  cardiovascular disease. Mounjaro (tirzepatide), a GIP/GLP-1 dual receptor agonist, was  compared to Trulicity (dulaglutide), a GLP-1 receptor agonist that showed a definitive cardiovascular benefit in the REWIND study. In SURPASS-CVOT, Mounjaro achieved the primary  objective by demonstrating a non-inferior rate of major adverse cardiovascular events (MACE 3), including cardiovascular death, heart attack or stroke vs. Trulicity. In addition, while not  controlled for multiplicity-adjusted type-1 error, Mounjaro showed improvements on key  measures of A1C, weight, renal function and all-cause mortality. The trial, which enrolled more  than 13,000 participants across 30 countries and lasted more than four and a half years, is the  largest and longest study of tirzepatide to date. 

“Cardiovascular disease continues to be the leading cause of death among individuals with type  2 diabetes,” said Winselow Tucker, President and General Manager, Eli Lilly and Company  (India). “The SURPASS-CVOT trials highlight that Mounjaro maintains the cardioprotective  effects seen with Trulicity, a GLP-1 receptor agonist, while offering additional advantages such  as a slower eGFR decline and a lower mortality rate. These results further support Mounjaro’s  potential as a front-line therapy for people managing both type 2 diabetes and cardiovascular  conditions."

In the trial, the risk of cardiovascular death, heart attack, or stroke was 8% lower for Mounjaro  vs. Trulicity (hazard ratio: 0.92; 95.3% CI: 0.83 to 1.01), meeting the prespecified criteria for  non-inferiority (upper limit of 95.3% CI of the hazard ratio < 1.05).1,2 Mounjaro showed  consistent results across all three components of the MACE-3 composite endpoint. The rate of  all-cause mortality was 16% lower for Mounjaro vs. Trulicity (hazard ratio: 0.84; 95.0% CI: 0.75 to 0.94).1,3 

A pre-specified indirect comparison analysis of matched patient-level data from the REWIND and SURPASS-CVOT studies found that Mounjaro reduced the risk of MACE-3 by 28% (hazard  ratio: 0.72; 95.0% CI: 0.55 to 0.94) and all-cause mortality by 39% (hazard ratio: 0.61; 95.0% CI:  0.45 to 0.82) compared to a putative placebo.3,4 In another key pre-specified analysis of  participants with high or very-high risk of chronic kidney disease, Mounjaro slowed eGFR  decline by 3.54 mL/min/1.73 m2 at 36 months vs. Trulicity (95.0% CI: 2.57 to 4.50).3,5,6 

Primary and Select Secondary Endpoints:

Mounjaro (tirzepatide) 

Trulicity (dulaglutide)

Primary Endpoint

Time-to-first  

occurrence of  

MACE-3i

Hazard Ratio = 0.92 

95.3%ii CI: 0.83 to 1.01iii 

p = 0.086

Secondary Endpoints

Time to all-cause  deathi 

Hazard Ratio = 0.84 

95.0% CI: 0.75 to 0.94 

p = 0.002iv

Change in eGFR in  chronic kidney  

disease population from mean baseline  of 53.4 mL/min/1.73  m2 at 36 monthsv

-4.97 mL/min/1.73 m2

-8.51 mL/min/1.73 m2

Estimated treatment difference: 

3.54 mL/min/1.73 m2(95.0% CI: 2.57 to 4.50) 

p = 0.001iv

A1C reduction from  mean baseline of  8.39% at 36  

monthsv,vi

1.73% 

0.90%

Estimated treatment difference: 

-0.83% (95.0% CI: -0.88 to -0.78) 

p < 0.001iv

-12.06% (-11.43 kg / -25.20 lbs) 

-4.95% (-4.65 kg / -10.25 lbs)

Change from mean  baseline of 92.6 kg  (204.15 lbs) in body  weight at 36  

monthsv,vi

Estimated treatment difference: 

-7.1% (95.0% CI: -7.4 to -6.8) 

p < 0.001iv

iTime-to-first event analysis using Cox proportional hazard model.  

ii95.3% CI reported due to type 1 error rate adjusted for efficacy interim analysis. iiiBoundary for non-inferiority statistical significance < 1.05.  

ivNot controlled for multiplicity-adjusted type 1 error rate. 

vBaseline values represent the overall mean combining the Mounjaro and Trulicity groups. viAnalysis of change from baseline to 36 months using ANCOVA model with multiple imputation  of missing data. 

In the trial, Mounjaro also led to greater improvements in A1C, weight and cardiovascular  biomarkers, including lipids and systolic blood pressure, compared to Trulicity.3 The safety and  tolerability of Mounjaro and Trulicity were generally consistent with their established profiles. The most commonly reported adverse events in SURPASS-CVOT for both Mounjaro and Trulicity  were gastrointestinal-related, generally mild-to-moderate in severity, and mostly resolved after  dose escalation was complete. During the trial, 13.3% of participants taking Mounjaro  discontinued treatment due to adverse events, compared to 10.2% of participants taking  Trulicity.7 

Detailed results for SURPASS-CVOT will be presented at the European Association for the Study  of Diabetes (EASD) Annual Meeting 2025 in September and published in a peer-reviewed  journal. Lilly plans to submit these data to global regulatory authorities by the end of this year.  

About SURPASS-CVOT  

SURPASS-CVOT (Cardiovascular Outcomes Trial) (NCT04255433) was an event-driven,  randomized, double-blind, parallel group Phase 3 trial evaluating the efficacy and safety of  Mounjaro (tirzepatide) compared with Trulicity (dulaglutide) in adults with type 2 diabetes and  established atherosclerotic cardiovascular disease, which lasted approximately five years (with a  median follow-up of four years). In the trial, 13,299 participants were randomized 1:1 across 640  sites in 30 countries to receive the maximum tolerated dose (MTD) of Mounjaro (5 mg, 10 mg or  15 mg) or Trulicity (1.5 mg) administered subcutaneously once weekly. The primary objective of  the trial was to demonstrate that Mounjaro provided a non-inferior reduction in the risk of  major adverse cardiovascular events (MACE-3)—a composite of cardiovascular death, heart  attack, or stroke—compared to Trulicity. SURPASS-CVOT utilized MTD of 5 mg, 10 mg or 15 mg 

once weekly. The starting dose of 2.5 mg Mounjaro was increased by 2.5 mg every four weeks  until MTD was achieved. Participants who tolerated 15 mg continued on 15 mg as their MTD.  Participants who tolerated 10 mg but did not tolerate 15 mg continued on 10 mg as their MTD,  and participants who tolerated 5 mg but did not tolerate 10 mg continued on 5 mg as their MTD. 

About REWIND (2019) 

REWIND (NCT01394952) was a multicenter, randomized, double-blind, placebo-controlled trial,  published in 2019, designed to assess the effect of Trulicity (1.5 mg) compared to placebo in  adults with type 2 diabetes with and without established cardiovascular disease. The primary  cardiovascular outcome was the first occurrence of MACE-3. Secondary outcomes include each  component of the primary composite CV outcome, a composite clinical microvascular outcome  comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring  hospitalization or an urgent heart failure visit, and all-cause mortality. In the trial, 9,901  participants from 24 countries had a mean duration of diabetes of 10.5 years and a median  baseline A1C of 7.2%.  

About tirzepatide 

Tirzepatide is a once-weekly dual GIP (glucose-dependent insulinotropic polypeptide) receptor  and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that  activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP  and GLP-1 receptors are found in areas of the human brain important for appetite regulation.  Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting  appetite. Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in  obesity (MMO) are ongoing. 

Tirzepatide has been approved by the U.S. FDA as Mounjaro for adults with type 2 diabetes to  improve glycemic control, and as Zepbound for adults with obesity, or some adults who are  overweight and also have at least one weight-related medical problem, to lose weight and keep  it off. Additionally, Zepbound is FDA-approved to treat adults with moderate-to-severe  obstructive sleep apnea and obesity. Tirzepatide is also approved as Mounjaro in some  countries outside the U.S. for adults with type 2 diabetes, obesity or those who are overweight  who also have a weight-related comorbid condition. Both Mounjaro and Zepbound should be  used in combination with diet and exercise. 

Endnotes and References

1. Time-to-first event analysis using Cox proportional hazard model.  
2. 95.3% CI reported due to type 1 error rate adjusted for efficacy interim analysis. 3. Not controlled for multiplicity-adjusted type 1 error rate. 
3. Hazard ratio (HR) estimates related to indirect comparison used Cox proportional hazard  model adjusted with stabilized inverse-probability weight based on probability of a  patient belonging to SURPASS-CVOT given baseline covariates. 
4. Analysis of change from baseline to 36 months using ANCOVA model with multiple  imputation of missing data. 
5. Subgroup defined as patients with high or very-high risk chronic kidney disease, per  KDIGO 2025 guidelines. Kidney function was assessed by change in eGFR using the CKD EPI Creatinine-Cystatin 2021 equation over 36 months. 
6. Percentage calculated based on modified intent-to-treat population. 

About Lilly 

Lilly is a medicine company turning science into healing to make life better for people around  the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our  medicines help tens of millions of people across the globe. Harnessing the power of  biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new  discoveries to solve some of the world’s most significant health challenges: redefining diabetes  care; treating obesity and curtailing its most devastating long-term effects; advancing the fight  against Alzheimer’s disease; providing solutions to some of the most debilitating immune  system disorders; and transforming the most difficult-to-treat cancers into manageable  diseases. With each step toward a healthier world, we’re motivated by one thing: making life  better for millions more people. That includes delivering innovative clinical trials that reflect the  diversity of our world and working to ensure our medicines are accessible and affordable. To  learn more, visit Home | Lilly India follow us on LinkedIn.